Submissions for variant NM_198253.3(TERT):c.316G>T (p.Gly106Trp)

dbSNP: rs1751265277

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001776697	SCV002013453	uncertain significance	not provided	2021-05-07	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies demonstrate reduced telomerase activity (Terada 2020); Reported in individuals with DC and a positive family history (Yamaguchi 2015), however, additional clinical and segregation information was not included; This variant is associated with the following publications: (PMID: 32150348, 26329388)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003772116	SCV004606331	uncertain significance	Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis	2022-12-18	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TERT protein function. ClinVar contains an entry for this variant (Variation ID: 1320718). This missense change has been observed in individual(s) with clinical features of TERT associated conditions (PMID: 26329388, 32150348). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 106 of the TERT protein (p.Gly106Trp).